title: Acute skeletal muscle wasting in critical illness.
abstract: OBJECTIVE
  Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment.
  
  
  OBJECTIVE
  To perform a comprehensive prospective characterization of skeletal muscle wasting, defining the pathogenic roles of altered protein synthesis and breakdown.
  
  
  METHODS
  Sixty-three critically ill patients (59% male; mean age: 54.7 years [95% CI, 50.0-59.6 years]) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95% CI, 21.9-25.2) were prospectively recruited within 24 hours following intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay.
  
  
  METHODS
  Muscle loss was determined through serial ultrasound measurement of the rectus femoris cross-sectional area (CSA) on days 1, 3, 7, and 10. In a subset of patients, the fiber CSA area was quantified along with the ratio of protein to DNA on days 1 and 7. Histopathological analysis was performed. In addition, muscle protein synthesis, breakdown rates, and respective signaling pathways were characterized.
  
  
  RESULTS
  There were significant reductions in the rectus femoris CSA observed at day 10 (−17.7% [95% CI, −25.9% to 8.1%]; P < .001). In the 28 patients assessed by all 3 measurement methods on days 1 and 7, the rectus femoris CSA decreased by 10.3% (95% CI, 6.1% to 14.5%), the fiber CSA by 17.5% (95% CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5% (95% CI, 13.4% to 45.6%). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure by day 7 (−15.7%; 95% CI, −27.7% to 11.4%) compared with single organ failure (−3.0%; 95% CI, −5.3% to 2.1%) (P < .001), even by day 3 (−8.7% [95% CI, −59.3% to 50.6%] vs −1.8% [95% CI, −12.3% to 10.5%], respectively; P = .03). Myofiber necrosis occurred in 20 of 37 patients (54.1%). Protein synthesis measured by the muscle protein fractional synthetic rate was depressed in patients on day 1 (0.035%/hour; 95% CI, 0.023% to 0.047%/hour) compared with rates observed in fasted healthy controls (0.039%/hour; 95% CI, 0.029% to 0.048%/hour) (P = .57) and increased by day 7 (0.076% [95% CI, 0.032%-0.120%/hour]; P = .03) to rates associated with fed controls (0.065%/hour [95% CI, 0.049% to 0.080%/hour]; P = .30), independent of nutritional load. Leg protein breakdown remained elevated throughout the study (8.5 [95% CI, 4.7 to 12.3] to 10.6 [95% CI, 6.8 to 14.4] μmol of phenylalanine/min/ideal body weight × 100; P = .40). The pattern of intracellular signaling supported increased breakdown (n = 9, r = −0.83, P = .005) and decreased synthesis (n = 9, r = −0.69, P = .04).
  
  
  CONCLUSIONS
  Among these critically ill patients, muscle wasting occurred early and rapidly during the first week of critical illness and was more severe among those with multiorgan failure compared with single organ failure. These findings may provide insights into skeletal muscle wasting in critical illness.
authors.forename: Zudin A
authors.initials: ZA
authors.lastname: Puthucheary
authors.forename: Jaikitry
authors.initials: J
authors.lastname: Rawal
authors.forename: Mark
authors.initials: M
authors.lastname: McPhail
authors.forename: Bronwen
authors.initials: B
authors.lastname: Connolly
authors.forename: Gamunu
authors.initials: G
authors.lastname: Ratnayake
authors.forename: Pearl
authors.initials: P
authors.lastname: Chan
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hopkinson
authors.forename: Rahul
authors.initials: R
authors.lastname: Phadke
authors.forename: Rahul
authors.initials: R
authors.lastname: Padhke
authors.forename: Tracy
authors.initials: T
authors.lastname: Dew
authors.forename: Paul S
authors.initials: PS
authors.lastname: Sidhu
authors.forename: Cristiana
authors.initials: C
authors.lastname: Velloso
authors.forename: John
authors.initials: J
authors.lastname: Seymour
authors.forename: Chibeza C
authors.initials: CC
authors.lastname: Agley
authors.forename: Anna
authors.initials: A
authors.lastname: Selby
authors.forename: Marie
authors.initials: M
authors.lastname: Limb
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Edwards
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.forename: Anthea
authors.initials: A
authors.lastname: Rowlerson
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Rennie
authors.forename: John
authors.initials: J
authors.lastname: Moxham
authors.forename: Stephen D R
authors.initials: SD
authors.lastname: Harridge
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hart
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Montgomery
mesh_terms: D018806:APACHE; D016638:Critical Illness; D004247:DNA / Q000032:analysis; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000150:complications* / Q000503:physiopathology; D009336:Necrosis; D011446:Prospective Studies; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D052097:Quadriceps Muscle / Q000000981:diagnostic imaging / Q000473:pathology*; D013997:Time Factors; D014463:Ultrasonography; D019282:Wasting Syndrome
chemical_list: D011506:Proteins; D004247:DNA